Transcript

Joel Werner: Hi, and welcome to the Health Report. I'm Joel Werner.

What do you think the following things have in common; memorising times tables, being gracious in defeat on the football field, and a recipe for tasty lamingtons. Any idea? Well, they're all things I learned from my mum. Our mums do a lot for us, but did you know that before we're even born they help determine how well our immune system works. That story later in the show.

We also take a look at chronic kidney disease, and ask the question; do the doctors of the future have an anti-obesity bias?

But up first, antibiotic resistance is one of the most pressing health concerns in the world today. Very few new antibiotics are being developed, and those we do have are becoming less effective as bacteria breed resistance. But some exciting research out of Boston suggests that silver might be a silver bullet.

Jim Collins is Professor of Biomedical Engineering at Harvard University.

James Collins: We discovered that silver, which is in fact an ancient antimicrobial that was used millennia ago by ancient Egyptians and ancient Greeks, we showed that it can be used in very small trace amounts as basically an antibiotic booster. And our approach was instead of trying to come up with or discover a completely new antibiotic was instead as engineers we thought could we figure out ways to use what we already have to make our commonly used and existing antibiotic arsenal even stronger than it is at present.

Joel Werner: So can you take us through what you did? How did you couple the silver with the antibiotic?

James Collins: Well, what we initially did was we wanted to first use systems engineering approaches to better figure out what silver does to bacteria, and in using these approaches we uncovered that silver does basically two things. One, it will weaken the outer membrane, the protective layer of bacteria, making it more permeable to big antibiotics on the outside. Second, it will disrupt the internal biology of the bacteria, leading to oxidative stress which serves to weaken the bacteria, making them more susceptible to antibiotics. And so we then went to the next step and said could we harness these two features or exploit them by basically including a very small amount of silver in solution with the antibiotics that we initially delivered to bacteria in Petri dishes in our lab, and then we actually delivered the silver with antibiotics in treatments as part of mouse studies. We found across a range of conditions that these small non-toxic levels of silver could substantially boost the killing efficacy of the antibiotics.

Joel Werner: And this effect is seen with large-molecule antibiotics and on some of the toughest bacteria we have, the gram-negative bacteria that have protective cells.

James Collins: That's right, we primarily focus on the gram-negatives, and when you talk to colleagues in biotech and pharma, their number one challenge is how to combat multidrug resisting gram-negative bacteria. And so these are bacteria like E. coli that you have with gut infections and urinary tract infections, and pseudomonas bugs which are involved in lung infection, particularly in cystic fibrosis patients. Why they are problematic is they have this extra outer layer which prevents many antibiotics, particularly big ones like Vancomycin from getting in and exerting their lethal effects. We found that silver can weaken that outer membrane, that outer protective layer, enabling now large molecules like Vanco to get in.

Further, we showed that silver could go after sets of bacteria that are highly problematic, these so-called persisters that are these quasi-dormant cells that are thought now to underlie chronic and recurring infections. And we showed that silver again in very small trace amounts could enable commonly used antibiotics to wipe out these persisters, as well as to treat biofilm based infections which are highly problematic for really any medical device that you would put in the body, and this would include artificial hips, artificial knees or cardiac pacemakers.

Joel Werner: In terms of the toxicity of silver and I guess clinical translation, can you tell us how are you mitigated those effects?

James Collins: So silver, as I mentioned earlier, has been used for a long time, and one of its big challenges is that when you use it as a stand-alone antibacterial it can be quite toxic to the patient. And that is at the high concentrations needed for silver to be itself an antibacterial it can cause problematic side effects. We found that at the very small concentrations that we introduced where now we are using silver as the adjuvant or the antibiotic helper, we actually didn't encounter toxicity issues in the cell cultures and in the mouse models that we did.

As we think about moving this to human trials we'll need to initially run some small trials, one to assess the safety and the toxicity issues, and two to get toward efficacy. We are hopeful though that these small amounts will actually mitigate the potential toxicity issues, particularly if the silver would be used only for the most problematic infections and for relatively short treatment times, typically a one, two, three, maybe four-week course. And I think for that amount of time for the type of silver concentrations we would use, we are hopeful you wouldn't have significant side-effects.

Joel Werner: So where to next for you and the team? What's the next step in the research plan?

James Collins: We'd like to go in two different directions. One is we would like to move this toward early clinical trials in humans, and coupled with that we'd actually like to explore using smart biomaterials as well as nanoparticles as means to deliver in a very directed and controlled fashion the right amount of silver at the site of infection.